National Contact Point LIFESCIHEALTH Dr. Wilfried Diekmann Königswinterer Str. 522-524, 53227 Bonn

1. ERA-NET PathoGenoMics Constituent Assembly, October 13-15, 2004 Strategic supporting measures to raise synergies with the European framework programmes and to embedd PathoGenoMics into the European R&D Landscape National Contact Point LIFESCIHEALTH Dr. Wilfried Diekmann Königswinterer Str. 522-524, 53227 Bonn phone: +49 228 447 698, e-mail: wilfried.diekmann@dlr.de http://www.nks-lebenswissenschaften.de

2. Session overview W. DiekmannChair &Introduction Rationale and objectives for strategic support measures in PathoGenoMics Current FP6 project portfolio in pathogenomics Selected FP6 projects of high relevance to PathoGenoMics M. FroschEUROPATHOGENOMICS European Virtual Institue for Functional Genomics of Bacterial Pathogens (NoE) M. VicentemicroMatrix Workshop on strategies to address antimicrobial resistance through the exploitation of microbial genomics (SSA) Cooperation with European associations/societies and other stakeholders E. Ron FEMS Federation of Microbiological Societies International perspectives J. Hacker US Microbe Project Short statement on current developments

3. Integration • Biotechnology Action Plan FP National programmes project ↔ programme ↔ policy NoE ERA-NET Range regional/national ↔ transnational ↔ community Strategic supporting / supervision measures in ERA-NETs Rationale and objectives “Strategic Supervision“ in an ERA-NET means to support the coherent development of research activities with different range throughout Europe at all relevant levels of integration. This shall contribute to give a real meaning to the terms “subsidiarity“ and “variable geometry“ for a specific field of research.

4. Strategic supervision in PathoGenoMics, Task 9.4 Objectives and methodology → linking with NCP network, industrial associations, scientific societies, … → in particular at EU level as FP 6&7, ETIs; but also EUREKA, ESF, … set-up of powerful communication & multiplication networks for the ERA-NET continually observe programme design and project portfolios beyond the ERA-NET raise awareness and embedd the ERA-NET in the European research policy community (in particular beyond the partner countries and in relevant programme-making bodies, as e.g. EAG for FP7 preparation) supervision of international development (e.g. INCO target countries, trans-Atlantic cooperation) → develop perspectives for financial integration with other programmes → show international cooperation perspectives

5. a) Application-orientated genomic approaches Brain and diseases of the nervous system Cardiovascular disease, diabetes and rare diseases Human development and the ageing process Resis- tance to antibiotics and other drugs b) Application of knowledge and technologies in the field of genomics and biotechnology for health TP 1 Life Science, Genomics and Biotechnology for Health Programme structure and pathogenomics-relevant areas i) Advanced Genomics and its applications for health a) Fundamental knowledge & basic tools for functional genomics in all organisms Comparative genomics and population genetics Multidisciplinary functional genomics approaches to basic biological processes Gene expression and proteomics Bio-informatics Structural genomics Innovative research in post-genomics with high potential for application New preventive and therapeutic tools (somatic gene and cell therapies; stem cell and immunotherapies, etc.) New in vitro tests to replace animal experimentation New, safer,more effective drugs (incl. pharmaco-genomics) New diagnostics ii) Combating major diseases c) Poverty- related diseases b) Cancer • HIV / AIDS • Malaria • Tuberculosis

6. 1st Call (FP-2002-LIFESCIHEALTH, deadline: 25.03.2003) Selected pathogenomics-relevant areas

7. FP6 project portfolio in pathogenomics TP LSH, Fundamental Genomics, Outcome 1st Call Bacterial stress management relevant to infectious diseases and biopharma-ceuticals (BACELL HEALTH) –STREP, retained for funding Integrated study of the response of Gram-positive bacteria to stresses encountered by pathogens during infection and by industrial strains during industrial bioprocesses: understand and model regulatory networks/processes that comprise cell stress management systems identify key targets for novel anti-infectives and improving industrial bioprocesses Species: Bacillus subtilis, B. anthracis, B. cereus; Listeria monocytogenes, Staphylococcus aureus, Streptococcus pneumoniae Coordination: University Newcastle, UK

8. FP6 project portfolio in pathogenomics TP LSH, Applied Genomics, Outcome 1st Call Development of New Gyrase Inhibitors by combinatorial biosynthesis (COMBIGYRASE) –STREP, retained for funding Generation of novel inhibitors of gyrase and topoisomerase IV, in particular of the aminocoumarin and cyclothialidine type engineering complete biosynthetic pathways of natural inhibitors cloning and sequencing of complete gene clusters Species: Streptomyces spec. Methodology: Biophysics, X-ray crystallography, enzyme and antibacterial assays, animal experimentation Coordination: University Tübingen, DE

9. FP6 project portfolio in pathogenomics TP LSH, Major Diseases, Outcome 1st Call Combating resistance to antibiotics by broadening the knowledge on molecular mechanisms behind resistance to inhibitors of cell wall synthesis (COBRA) –STREP, retained for funding Elucidation of molecular mechanisms of resistance to inhibitors of cell wall synthesis in bacteria responsible for severe nosocomial and community-aquired infections: indepth understanding of resistance mechanisms based on ß-lactamases, penicillin-binding proteins, t-RNAdependent ligases, and other principles assess the modification of structure, function, dynamics of relevant pathways develop novel diagnostic and therapeutic tools Species: Pseudomonas, Acinobacter, S. pneumoniae, S. aureus, Enterococcus Methodology: structural genomics, crystallography, biochemistry, clinical microbiology, genetics Coordination: INSERM, FR

10. FP6 project portfolio in pathogenomics TP LSH, Major Diseases, Outcome 1st Call Molecular mechanisms of resistance, virulence and epidemicity in Streptococcus pneumoniae (PREVIS) –STREP, retained for funding Identification of bacterial genetic determinants and host factors associated with invasise disease, drug resistant pneumococcal clones and spread of epidemic S. pneumoniae clones frequency and clonal types of drug resistant and drug susceptible pneumococci old age homes and AIDS hospice as ecological reservoirs of resistant strains transcriptional profiling involving DNA microarrays sequencing of S. mitis, a frequent source of gene fragments resulting in resistance threshhold levels of antibiotic consumption in the community Species: Streptococcus pneumoniae Methodology: genomics, transcriptomics, clinical microbiology Coordination: Swedish Institute for Infectious Disease Control, SE

11. FP6 project portfolio in pathogenomics TP LSH, Major Diseases, Outcome 1st Call Workshop on strategies to address antimicrobial resistance through the exploitation of microbial genomics (micro MATRIX) –SSA, retained for funding Workshop to organise the European expertise needed to further apply functional genomics for fighting antimicrobial resistance: reveal novel anti-microbial targets discover new antibiotics understand the controls required to avoid the emergence of resistances discover regulatory notes and structural elements essential for resistance form a framework of leading experts and a concerted approach for further research Methodology: gene expression, physiology, stress response, adhesion, pathogenesis, and resistance mechanisms, Coordination: Consejo Superior de Investigaciones Científicas (CSIC), ES

12. FP6 project portfolio in pathogenomics TP LSH, Poverty-related diseases, Outcome 1st Call An Integrated project for the design and testing of vaccine candidates against tuberculosis: Identification, development and clinical studies (TB-VAC) –IP, retained for funding Development of improved TB vaccines, particularly for the young adult population: identify and develop novel vaccines or antigen components optimize the delivery and composition of candidate vaccines evaluate candidate vaccines in animal models as well as in Phase I clinical trials GMP production of vaccine candidates Coordination: Institut Pasteur, FR

13. 2nd Call (FP-2003-LIFESCIHEALTH-I, deadline: 13.11.2003) Selected pathogenomics-relevant areas

14. 2nd Call (FP-2003-LIFESCIHEALTH-3, deadline 24.03.2004) Selected pathogenomics-relevant areas

15. FP6 project portfolio in pathogenomics TP LSH, Fundamental Genomics, Outcome 2nd Call Genetics of Sepsis in Europe (GenOSept) - STREP, retained for funding Multidisciplinary fundamental genomics approach to examine genetic predisposition to sepsis (life threatening infection) identify candidate genes including those controlling programmed cell death epidemiology studies of genetic disposition to sepsis-related mortality and morbidity in European intensive care units gender-related aspects of sepsis patients target risk subpopulations Methodology: gene expression, structural genomics, population genetics, genetic epidemiology, biometrics, high-throughput genotyping Coordination: European Society of Intensive Care Medicine (ESICM), BE

16. FP6 project portfolio in pathogenomics TP LSH, Functional Genomics, Outcome 2nd Call Functional genomic characterization of the bacterial Tat complex as a nanomachine for biopharmaceutical production and a target for novel anti-infectives (Tat machine) –STREP, retained for funding Multidisciplinary functional genomic characterization of the Twin-arginine translocation (Tat) machinery, which is a widely conserved system for bacterial protein secretion: improve and use the Tat nanomachine for biopharmaceutical production use the Tat nanomachine of major Gram-positive and -negative pathogens as potential target for novel anti-infectives Species: Bacillus, E. coli, Streptomyces, E. coli O 157, Pseudomonas aeruginosa Methodology : bioinformatics, comparative and structural geniomics, proteomics Coordination: University of Groningen, NL

17. FP6 project portfolio in pathogenomics TP LSH, Applied Genomics, Outcome 2nd Call European Virtual Institute for Functional Genomics of Bacterial Pathogens – (EUROPATHOGENOMICS/EPG) - NoE, retained for funding Network to form a durable alliance of the best pathogenomics research capacities bring together relevant epidemiological, basic and applied research stimulate collaborative, multidisciplinary research activities foster biotechnological applications and technology transfer (in terms of innovative diagnostic tools, anti-infectious agents, antigens and/or host defence mechanisms) Methodology : molecular biology, immunology, cell biology, structural biology Coordination: University of Würzburg, DE Nationales Kompetenzzentrum “Genomanalyse pathogener Mikroorganismen“

18. FP6 project portfolio in pathogenomics TP LSH, Applied Genomics, Outcome 2nd Call Electrical bio sensor arrays for analyses of harmful microorganisms and microbial toxins (eBIOSENSE) - STREP, retained for funding Advanced technology platform for analysis of food and water born harmful microorganisms and /or their toxins (e.g. mycotoxins): electric biochip arrays enabling the parallel and simultaneous identification of nucleic acids, microbial proteins and toxins (based on nm-sized interdigital gold electrodes) design of portable instruments furnished with disposable chips Species: Escherichia coli (STEG, ETEC, EHEC), Salmonella enteridis, Bacillus cereus, Staphylococci, Legionella Methodology : genomics, proteomics,bioinformatics, advanced silicon and microsystem technologies Coordination: Kungliga Tekniska Högskolan, SE

19. FP6 project portfolio in pathogenomics TP LSH, Applied Genomics, Outcome 2nd Call SLIC-Biosensors in Molecular Diagnostics: Nanotechnology for the analysis of species-specific microbial transcripts (SLIC) - STREP, retained for funding Development of alternative technologies for direct genotyping and/or screening of the transcriptome for multiparametric testing systems usable in clinical diagnostics: use of tmRNA transcripts of the bacterial ssrA gene based on a self-assembled lipid bilayer membrane that integrates a synthetic ligand-gated ion-channel (so-called SLIC-Nanobiosystem) monitoring via electrical impedance sopectroscopy ultra-sensitive qunatification and identification of bacterial species in a single homogenous assay format prototypes of miniaturized/compact and cost-effective instruments Methodology: transcriptomics, genomics, electronics Coordination: Ayanda Biosystems, CH

20. FP6 project portfolio in pathogenomics TP LSH, Applied Genomics, Outcome 2nd Call The fungal cell wall as a target for antifungal therapies (FUNGWALL) - STREP, retained for funding Research programme on core cell wall complexes which are common to all pathogenic fungi: characterise the enzymes and reactions associated with chitin synthesis, glucan branching and cross-linking of chitin and 1-3 glucan signalling mechanisms allowing fungi to adapt to/survive cell wall damages define novel antifungal targets and compounds effecting cell wall integrity Species: Candida albicans, Aspergillus fumigatus Coordination: Institut Pasteur, FR

21. FP6 project portfolio in pathogenomics TP LSH, Major Diseases, Outcome 2nd Call Integrating genomics-based applications to exploit Actinomyces as a resource for new antibiotics (ActinoGEN) - IP, retained for funding Genomics-based approach to exploit hitherto overlooked genetic resources for new antibiotics: assess new biosynthetic pathways from diverse species activate cryptic pathways from well-characterised species engineer novel hybrid antibiotics by combinatorial biosynthesis Methodology: multidiscipliar post-genomics, biochemistry, physiology, chemistry Species: Actinomycetes, in particular Streptomyces coelicolor (genome completely sequenced) Coordination: University of Wales Swansea, UK

22. FP6 project portfolio in pathogenomics TP LSH, Major Diseases, Outcome 2nd Call Inhibition of new targets for fighting antibiotic resistance (EUR-INTAFAR) - IP, retained for funding Coherent set of converging approaches to study and design novel targets (i.e. enzyme inhibitors and/or agents perturbing protein-protein interactions) interfering with bacterial peptidoglycan biosynthesis and cell morphogenesis: inhibitors for penicillin-resistant transpeptidases inhibitors of the glycosyltransferase domain of class A penicillin-binding proteins inhibiting synthesis and transport of cell wall subunits at the plasma membrane interfering cell morphogenesis and its regulation Methodology: biotechnology, bacterial physiology, cell biology Species: streptocooci, staphylococci, enterococci, chlamydiae Coordination: Université de Liège, BE

23. FP6 project portfolio in pathogenomics TP LSH, Major Diseases, Outcome 2nd Call New methods of treatment of antibiotic-resistant pneumococcal disease (PNEUMOPEP) - STREP, retained for funding New targets/lead compounds as well as adjunctive therapy and drug delivery approaches against pneumonia and meningitis (including the related acute toxaemia caused by pro-inflammatory pneumococcal toxins as e.g. pneumolysin): targets: pneumolysin; cell surface proteinases involved in adhesion and invasion treatment approach based on binding peptides and small molecules isolated from large phage display libraries drug formulation in chitosan for nasal delivery pharmacological testsin animal models of pneumonia, bacteraemia and meningitis, Species: multiresistant strains of Streptococcus pneumoniae Coordination: University of Leicester, UK

24. FP6 project portfolio in pathogenomics TP LSH, Major Diseases, Outcome 2nd Call Antimicrobials by Immune Stimulation (AMIS) - STREP, retained for funding Innovative approach to use the strength of the human immune system to design new antimicrobial drugs and/or to broaden the approaches in therapeutic intervention: Target: antimicrobial proteins that trigger inflammatory signals (i.e. in one single molecule) Screen and modify novel “dual mode of action effector molecules” as potential drug candidates Species: various extra- and intracellular bacteria Coordination: University Medical Centre Utrecht, NL

25. FP6 project portfolio in pathogenomics TP LSH, Poverty-related diseases, Outcome 2nd Call Finding promising drug candidates against tuberculosis with multidisciplinary protocol based non-conventional search (scrIN-SILICO) –STREP, retained for funding Development of a protocol capable of identifying novel drug binding sites and novel drug-protein complexes of Mycobacterium tuberculosis proteins consisting of: a method to identify surface indentation patterns in protein 3D structures structural & molecular biology protocol for examining promising drug- protein fit pairs Coordination: Eotvos Lorand Tudomanyegyetem, HU

26. FP6 project portfolio in pathogenomics TP LSH, Poverty-related diseases, Outcome 2nd Call Genome- and HLA- wide scanning and validation of cytotoxic CD8 T cell responses against Mycobacterium tuberculosis(VACCINES4TB) –STREP, retained for funding Genomics/proteomics based platform for antigen- and epitope-discovery with relevance to human immune CD8 cytotoxic T cells responses against M. tuberculosis Methodology: high-throughput methods from immunology and bioinformatics Coordination: Technical University of Denmark, DK

27. FP6 project portfolio in pathogenomics TP LSH, Poverty-related diseases, Outcome 2nd Call Molecular markers of M. tuberculosis early interactions with host phagocytes (MM-TB) –STREP, retained for funding Comparative genomics approach to develop new markers of protection and to identify novel molecular patterns, both in the microbe and in the host cells, being associated with early interactions between M. tuberculosis and phagocytic cells microarrays to simultaneously study the entire expressed genomes of both the mammalian host (macrophages, dendritic cells) and the microbial parasite during their interaction reveal patterns of the induced gene expression novel targets for vaccine design molecular markers and pathways associated with protection Methodology: transcriptional profiling approaches Coordination: Technical University of Denmark, DK

28. FP6 project portfolio in pathogenomics TP LSH, Poverty-related diseases, Outcome 2nd Call Development of a molecular platform for the simultaneous detection of Mycobacterium tuberculosis resistance to rifampicin and fluoroquinolones (TB-DRUG OLIGOCOLOR) –STREP, retained for funding Molecular platform for the identification of Mycobacterium tuberculosis in clinical specimens and simultaneous detection of resistance to rifampicin & fluoroquinolones: Methodology: microplates, enzymatic chromogen detection systems Coordination: Institute of Tropical Medicine, BE

29. FP6 project portfolio in pathogenomics TP LSH, Poverty-related diseases, Outcome 2nd Call Strategy for characterisation of the worldwide population structure of Mycobacterium tuberculosis in relation to the efficacy of new tuberculosis vaccines (TB World Collection) –SSA, retained for funding Preparing a strategy for collecting isolates in a non-biased way in order to characterise the worldwide population structure of M. tuberculosis: meeting of relevant specialists and contacts from developing countries develop a strategy for determining the evolutionary divergence worldwide standard set of most significant strains regarding the current TB epidemic Coordination: National Institute of Public Health and the Environment, NL

30. FP6 project portfolio in pathogenomics TP LSH, Poverty-related diseases, Outcome 2nd Call The diversity of Mycobacterium tuberculosis strains in China: tracing the origins of the worldwide dispersion of the multidrug-resistant Beijing genotype (TB China) –SSA, retained for funding Organization of the analysis of a large collection of strains (3000) from the 31 Provinces of China: genotyping and multidrug-resistance (MDR) assessment clinical information as e.g. BCG status, age and gender of the patients technical knowledge exchange to Chinese laboratories Coordination: University of Paris, FR

31. FP6 project portfolio in pathogenomics TP LSH, Poverty-related diseases, Outcome 2nd Call Establishing a TB Treatment Efficacy Marker (TB Treatment Marker) –SSA, retained for funding Strategy development for monitoring TB progression and the efficacy of TB treatment as well as for guiding clinical decision-making in TB management blood plasma protein suPAR level as a potential useful marker pilot study in Guinea-Bissau (one of the highest TB incidences in the world !) Coordination: ViroGates ApS, FR

32. 3rd Call (FP-2004-LIFESCIHEALTH-5, deadline: 16.11.2004) Selected pathogenomics-relevant areas